A5021660069- SARS-CoV-2 and COVID-19 Research
- Bacteriophages and microbial interactions
- Endoplasmic Reticulum Stress and Disease
- Cancer Research and Treatments
- SARS-CoV-2 detection and testing
- Viral gastroenteritis research and epidemiology
- Bacillus and Francisella bacterial research
- CRISPR and Genetic Engineering
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Advanced Biosensing Techniques and Applications
- Nanopore and Nanochannel Transport Studies
- Molecular Communication and Nanonetworks
- Atomic and Subatomic Physics Research
- COVID-19 Clinical Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Heat shock proteins research
- Microbial Inactivation Methods
- Phagocytosis and Immune Regulation
- bioluminescence and chemiluminescence research
- RNA regulation and disease
- Redox biology and oxidative stress
- ATP Synthase and ATPases Research
University of British Columbia
2021-2023
Dana-Farber Cancer Institute
2019-2020
Boston VA Research Institute
2019-2020
Harvard University
2019-2020
Icahn School of Medicine at Mount Sinai
2019
Northeastern University
2019
The University of Texas at Austin
1982
The University of Texas Health Science Center at San Antonio
1982
Southern Methodist University
1982
The University of Texas Health Science Center at Houston
1982
The newly reported Omicron variant is poised to replace Delta as the most prevalent SARS-CoV-2 across world. Cryo-EM structural analysis of spike protein in complex with human ACE2 reveals new salt bridges and hydrogen bonds formed by mutated residues R493, S496 R498 RBD ACE2. These interactions appear compensate for other mutations such K417N known reduce binding affinity, resulting similar biochemical affinities variants. Neutralization assays show that pseudoviruses displaying exhibit...
The recently reported "UK variant" (B.1.1.7) of SARS-CoV-2 is thought to be more infectious than previously circulating strains as a result several changes, including the N501Y mutation. We present 2.9-Å resolution cryo-electron microscopy (cryo-EM) structure complex between ACE2 receptor and spike protein ectodomains that shows Y501 inserted into cavity at binding interface near Y41 ACE2. This additional interaction provides structural explanation for increased affinity mutant, likely...
The Delta and Kappa variants of SARS-CoV-2 co-emerged in India late 2020, with the variant underlying resurgence COVID-19, even countries high vaccination rates. In this study, we assess structural biochemical aspects viral fitness for these two using cryo-electron microscopy (cryo-EM), ACE2-binding antibody neutralization analyses. Both demonstrate escape antibodies targeting N-terminal domain, an important immune hotspot neutralizing epitopes. Compared to wild-type lineages, spike proteins...
The recently emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Beta (B.1.351) and Gamma (P.1) variants of concern (VoCs) include a key mutation (N501Y) found in the Alpha (B.1.1.7) variant that enhances affinity spike protein for its receptor, angiotensin-converting enzyme 2 (ACE2). Additional mutations are these at residues 417 484 appear to promote antibody evasion. In contrast, Epsilon (B.1.427/429) lack N501Y yet exhibit We have engineered proteins express receptor...
Abstract Mutations in the spike glycoproteins of SARS-CoV-2 variants concern have independently been shown to enhance aspects protein fitness. Here, we describe an antibody fragment (V H ab6) that neutralizes all major including recently emerged BA.1 and BA.2 Omicron subvariants, with a unique mode binding revealed by cryo-EM studies. Further, provide comparative analysis mutational effects within previously variant spikes identify structural role mutations NTD RBD evading neutralization....
Abstract Most human protein-coding genes are expressed as multiple isoforms, which greatly expands the functional repertoire of encoded proteome. While at least one reliable open reading frame (ORF) model has been assigned for every coding gene, majority alternative isoforms remains uncharacterized due to (i) vast differences overall levels between different from common genes, and (ii) difficulty obtaining full-length transcript sequences. Here, we present ORF Capture-Seq (OCS), a flexible...
The newly reported Omicron variant is poised to replace Delta as the most rapidly spread SARS-CoV-2 across world. Cryo-EM structural analysis of spike protein in complex with human ACE2 reveals new salt bridges and hydrogen bonds formed by mutated residues R493, S496 R498 RBD ACE2. These interactions appear compensate for other mutations such K417N known reduce binding affinity, explaining our finding similar biochemical affinities variants. Neutralization assays show that pseudoviruses...
The interaction between putidaredoxin and cytochrome P-450,,, has been studied by equilibrium kinetic techniques.The of oxidized P-450,-was investigated using a modified version the gel filtration technique developed Hummel Dreyer (Hummel,
The human AAA+ ATPase p97, also known as valosin-containing protein, a potential target for cancer therapeutics, plays vital role in the clearing of misfolded proteins. p97 dysfunction is to play crucial several neurodegenerative disorders, such MultiSystem Proteinopathy 1 (MSP-1) and Familial Amyotrophic Lateral Sclerosis (ALS). However, structural basis its diseases remains elusive. Here, we present cryo-EM analyses four disease mutants p97R155H, p97R191Q, p97A232E, p97D592N, well...
Abstract The recently reported “UK variant” of SARS-CoV-2 is thought to be more infectious than previously circulating strains as a result several changes, including the N501Y mutation. We present 2.9-Å resolution cryo-EM structure complex between ACE2 receptor and spike protein ectodomains that shows Y501 inserted into cavity at binding interface near Y41 ACE2. additional interactions in increased affinity for mutant, accounting its infectivity. However, this mutation does not large...
Abstract The Delta and Kappa variants of SARS-CoV-2 co-emerged in India late 2020, with the variant underlying resurgence COVID-19, even countries high vaccination rates. In this study, we assess structural biochemical aspects viral fitness for these two using cryo-electron microscopy (cryo-EM), ACE2-binding antibody neutralization analyses. Both demonstrate escape antibodies targeting N-terminal domain, an important immune hotspot neutralizing epitopes. Compared to wild-type lineages, spike...
Abstract Most human protein-coding genes are expressed as multiple isoforms. This in turn greatly expands the functional repertoire of encoded proteome. While at least one reliable open reading frame (ORF) model has been assigned for every gene, majority alternative isoforms remains uncharacterized experimentally. is primarily due to: i) vast differences overall levels between different from common genes, and ii) difficulty obtaining contiguous full-length ORF sequences. Here, we present...
Summary The recently emerged SARS-CoV-2 South African (B. 1.351) and Brazil/Japan (P.1) variants of concern (VoCs) include a key mutation (N501Y) found in the UK variant that enhances affinity spike protein for its receptor, ACE2. Additional mutations are these at residues 417 484 appear to promote antibody evasion. In contrast, Californian VoCs (B.1.427/429) lack N501Y mutation, yet exhibit We engineered proteins express RBD VoC either isolation, or different combinations, analyzed effects...
Abstract Mutations in the spike glycoproteins of SARS-CoV-2 variants concern have independently been shown to enhance aspects protein fitness. Here, we report discovery a novel antibody fragment (V H ab6) that neutralizes all major variants, with unique mode binding revealed by cryo-EM studies. Further, provide comparative analysis mutational effects within variant spikes and identify structural role mutations NTD RBD evading neutralization. Our shows highly mutated Gamma N-terminal domain...
ABSTRACT The human AAA ATPase p97, a potential cancer target, plays vital role in clearing misfolded proteins. p97 dysfunction is also known to play crucial several neurodegenerative disorders. Here, we present cryo-EM structural analyses of four disease mutants R155H , R191Q A232E D592N as well E470D implicated resistance the drug CB-5083. These structures demonstrate that mutations affect nucleotide-driven allosteric activation by predominantly interfering with either coupling between D1...